title: Enhanced filopodium formation and stem-like phenotypes in a novel metastatic head and neck cancer cell model.
abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, and metastasis is the major cause of cancer-related mortality. Prevention or elimination of metastasis may improve the survival of cancer patients; however, the availability of systemic HNSCC cell model with which to investigate the mechanisms of metastasis is limited. In the present study, we established a set of metastatic cell lines from HNSCC cells. In combination with their low-tumorigenic and high-tumorigenic ancestor cell lines, a cell model containing cell lines with varying malignant characteristics was established. Transcriptome analysis revealed distinct signatures among the metastatic cell lines, in comparison to the ancestor cell lines. Signaling of GTPase RhoA and mammalian embryonic stem cell pluripotency were identified in the metastatic cells. Moreover, we examined the expression of genes related to epithelial-mesenchymal transition (EMT) (Snail, Slug, Twist, vimentin and fibronectin) and stemness (Oct4, Nanog and Bmi1). The capabilities of the cells for migration, invasion, spheroid formation and pulmonary colonization in nude mice were determined. Together, we demonstrated gain of Slug expression, filopodium formation and stem-like properties in metastatic HNSCC cells, rendering this model a powerful tool for the development of diagnostic biomarkers and identification of therapeutic targets for HNSCC.
authors.affiliation: Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan, R.O.C.
authors.forename: Yu-Syuan
authors.initials: YS
authors.lastname: Chen
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Huang
authors.forename: Shu-Hao
authors.initials: SH
authors.lastname: Chang
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Chang
authors.forename: Shou-Yen
authors.initials: SY
authors.lastname: Kao
authors.forename: Jeng-Fan
authors.initials: JF
authors.lastname: Lo
authors.forename: Pei-Fen
authors.initials: PF
authors.lastname: Su
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006258:Head and Neck Neoplasms; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011554:Pseudopodia / Q000378:metabolism / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000096:biosynthesis*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors